Systems and methods for indicating lifetime of an NO2-to-NO reactor cartridge used to deliver NO for inhalation therapy to a patient

ABSTRACT

The principles and embodiments of the present invention relate to methods and systems for safely providing NO to a recipient for inhalation therapy. There are many potential safety issues that may arise from using a reactor cartridge that converts NO2 to NO, including exhaustion of consumable reactants of the cartridge reactor. Accordingly, various embodiments of the present invention provide systems and methods of determining the remaining useful life of a NO2-to-NO reactor cartridge and/or a break-through of NO2, and providing an indication of the remaining useful life and/or break-through.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims the benefit under 35 U.S.C. § 119(e) to U.S.Provisional Application No. 61/996,798, filed May 14, 2014, the entirecontents of which are incorporated herein by reference in its entirety.

TECHNICAL FIELD

Principles and embodiments of the present invention relate generally tosystems and methods for determining, and/or indicating to users, theproper operation and remaining life of an NO₂-to-NO reactor cartridgefor delivering NO to a patient, in need thereof, for inhalation therapy.

BACKGROUND

A number of gases have been shown to have pharmaceutical action inhumans and animals. One such gas is Nitric Oxide (NO) that, wheninhaled, acts to dilate blood vessels in the lungs, improvingoxygenation of the blood and reducing pulmonary hypertension. In thefield of inhalation therapy for various pulmonary conditions such asacute pulmonary vasoconstriction, hypertension and thromboembolism, orinhalation injury, treatment has included the use of the therapeutic gasNO supplied from a gas cylinder. More specifically, this gaseous NO forinhalation therapy is supplied to a patient from a high pressure gascylinder containing NO. For example, such an approach is disclosed inU.S. Pat. No. 5,558,083 entitled “Nitric Oxide Delivery System”, whichis incorporated herein by reference in its entirety.

Unlike supplying NO for inhalation therapy from a high pressure NOcylinder; some have proposed supplying NO for inhalation therapy from asource of Nitrogen Dioxide (NO₂), which is toxic, and converting thistoxic NO₂ into NO using a “cartridge” or “reactor” (NO₂-to-NO reactorcartridge) at the patient's bedside. For example, such an approach isdisclosed in U.S. Pat. No. 7,560,076 (“the '076 Patent”) issued Jul. 14,2009 to Rounbehler et al., and assigned to GENO, LLC, which isincorporated herein by reference in its entirety. The NO₂-to-NO reactorcartridge in the '076 Patent is filled with a loosely packed powder of asurface-active material (e.g., silica) coated with an aqueous solutionof an antioxidant (e.g., aqueous ascorbic acid). Purportedly, thereactor receives NO₂ that passes through the loosely packed silicacoated with the aqueous ascorbic acid and undergoes a chemical reactionthat converts NO₂ to NO, which in turn exits the reactor cartridge andis then delivered to the patient.

Substantial patient safety and efficacy concerns arise from convertingtoxic NO₂ to NO at the patient's bedside as proposed because of at leastthe toxic nature of NO₂. For example, as pointed out in the '076 Patent,“unlike NO, the part per million levels of NO₂ gas is highly toxic ifinhaled and can form nitric and nitrous acid in the lungs.”

Compounding risks relating to such NO₂ to NO conversion at the patient'sbedside, the ability of these NO₂-to-NO reactor cartridges to convertNO₂ to NO exhausts as it uses a consumable reactant and this exhaustionresults in the breakthrough of toxic NO₂, which in turn may be deliveredto the patient. Without an indicator (e.g., dosage meter) to the user ofthe amount of lifetime remaining for the reactor as it exhausts, a userhas no way of confirming how much or little lifetime the reactor hasprior to at least breakthrough of toxic NO₂. This can force the user toguess how much lifetime the reactor has prior to at least breakthroughof toxic NO₂; However, factors impacting the lifetime of the reactorand/or breakthrough of toxic NO₂ may not be readily attainable by userobservation.

Further compounding risks relating to such NO₂-to-NO reactor cartridges,the ability of these reactors to convert NO₂ to NO (e.g., lifetime) canbecome compromised resulting in breakthrough of toxic NO₂ beingdelivered to the patient. For example, the reactor can be compromised bya channel that allows NO₂ flow through the reactor cartridge withoutconversion to NO as disclosed in U.S. Pat. No. 8,646,445 (“the '445Patent”) issued Feb. 11, 2014, to Fine et al., and assigned to GENO,LLC, which is incorporated herein by reference in its entirety. Aspointed out in the '445 patent, “Creation of a channel negates theeffect of the powder and renders the cartridge useless. This problem isso severe that a packed tube like this can only be used if the cartridgeis vertical.”

Another NO₂-to-NO reactor cartridge is discussed in U.S. Pat. No.8,607,785 (“the '785 Patent”) issued Dec. 17, 2013, to Fine et al., andassigned to GENO, LLC, which is incorporated herein by reference in itsentirety. Rather than a loosely packed reactor cartridge, the '785Patent discloses a porous solid structure, which provides a rigidstructure coated with an aqueous solution of an antioxidant. However,such a porous solid structure can be brittle and have its structuralintegrity compromised by sudden shocks or rough handling, as might occurin a clinical setting and/or by user error, handling of the conversionreactor, and environmental factors, to name a few. For example, crackscan be formed in the structure which can provide a channel allowing flowof NO₂ through the reactor without conversion to NO, which in turn maybe delivered to the patient. Further, cracks in the structure may not beobvious until a gas flow is applied and/or NO₂ breakthrough occurs. Inanother scenario, a crack in the porous solid structure may notinitially propagate all the way through the structure until sometimelater under routine usage, when a toxic NO₂ suddenly exits the reactorcartridge, which in turn may be delivered to the patient. Accordingly,such compromised reactors may have unforeseen shortened lifetimes.

The above are only a few of the exemplary scenarios which can result ina patient receiving toxic NO₂ using the proposed techniques ofconverting toxic NO₂ to NO at the patient's bedside using an exhaustiblereactor cartridge when lifetime of reactor is unknown to the user. Giventhe risk of serious injury or death associated with inhalation of NO₂along with compounding factors and/or failure modes which may not bereadily attainable by a user (e.g., reactor exhaustion, channeling,compromised reactors, NO₂ breakthrough, etc.) a need exists to providean indicator (e.g., dosage meter) to the user of the amount of lifetimeremaining for the reactor.

SUMMARY

There are several ways to address the above problems, includingmonitoring the use of the reactor(s), including indicators that visuallywarn a user of hazardous operating conditions, detectors that detect thepresence or absence of the chemical species of interest, and meters thatfollow the depletion and/or operation of the system in real time.

Principles and embodiment of the present invention relate to systems andmethods of determining the remaining useful life of a NO₂-to-NO reactorcartridge and/or a break-through of NO₂ at concentrations that mayseriously impact a patient's health.

Principles and embodiments of the present invention also relate to meansof monitoring the performance of an inhalation therapy system thatconverts NO₂ to NO comprising a source of NO₂, a conversion reactor, anda delivery member.

Principles and embodiments of the present invention also relate tosystems and methods of determining a significant and/or catastrophicbreak-through of NO₂ and preventing harmful or lethal doses of NO₂ fromreaching the inhalation therapy recipient.

Principles and embodiments of the present invention also relate to areactor meter that informs a user of the amount of remaining life of areactor and provides a safety check for proper reactor operation.

Principles and embodiments of the present invention also relate to asystem for safely delivering a supply of NO to a recipient, comprising agas source that supplies a gas, wherein the gas is NO₂ or NO, a gasconduit connected to and in fluid communication with the gas source, aNO₂-to-NO reactor cartridge connected to and in fluid communication withthe gas conduit, so as to allow gas to flow from the gas source to aninlet end of the conversion reactor, a means of monitoring thefunctioning of the conversion reactor operatively associated with theconversion reactor, a delivery conduit connected to and in fluidcommunication with an outlet end of the conversion reactor that allowsNO gas from the conversion reactor to flow to a recipient, a computer inelectronic communication with the monitoring means over a communicationpath, wherein the computer is configured to receive electronic signalsfrom the monitoring means and calculate a performance value forcomparison with a predetermined threshold value, and configured togenerate an actuating signal when the performance value falls below thethreshold value, a regulating means in electronic communication with thecomputer over a communication path, wherein the regulating means isconfigured to receive an actuating signal from the computer, and whereinthe regulating means halts the delivery of the gas to a recipient.

In addition, embodiments of the present invention relate to a systemwhich further comprises a flow meter for measuring the amount of gasentering the NO₂-to-NO reactor cartridge, a flow meter for measuring theamount of gas being delivered to the recipient, an NO₂ sensoroperationally associated with the delivery conduit to determine thepresence of an unacceptable level of NO₂ in the gas being directed tothe recipient.

Principles and embodiments of the present invention also relate to amethod of monitoring the performance of an NO₂-to-NO reactor cartridge,comprising, providing an NO2-to-NO reactor cartridge comprising aconversion media, incorporating one or more sensor probes into thereactor cartridge, wherein the one or more sensor probes are operativelyassociated with conversion media, providing a computer in electroniccommunication with the meter, providing at least one meter operativelyassociated with at least one sensor probe, and in electricalcommunication with the computer, detecting physical and/or chemicalcharacteristics of the conversion media with the sensor probe(s),measuring the detected physical and/or chemical characteristics with theoperatively associated meter, communicating the measured physical and/orchemical characteristics to the computer; monitoring the communicatedcharacteristics with the computer; and displaying the measuredcharacteristic(s) and/or activating and alarm.

BRIEF DESCRIPTION OF THE DRAWINGS

Further features of embodiment of the present invention, their natureand various advantages will become more apparent upon consideration ofthe following detailed description, taken in conjunction with theaccompanying drawings, which are also illustrative of the best modecontemplated by the applicants, and in which like reference charactersrefer to like parts throughout, where:

FIGS. 1A-1B illustrates exemplary inhalation therapy systems, inaccordance with exemplary embodiments of the present invention;

FIGS. 2A-2C illustrate an exemplary NO₂—NO conversion reactor, inaccordance with exemplary embodiments of the present invention;

FIGS. 3A-3C illustrate another exemplary NO₂—NO conversion reactor, inaccordance with exemplary embodiments of the present invention;

FIG. 4 illustrates an exemplary NO₂—NO reactor cartridge with integratedsensor probes, in accordance with exemplary embodiments of the presentinvention;

FIG. 5 illustrates an exemplary NO₂—NO reactor cartridge with integratedsensor probes, in accordance with exemplary embodiments of the presentinvention;

FIG. 6 illustrates an exemplary NO₂—NO reactor cartridge with amonolithic consumable conversion media, in accordance with exemplaryembodiments of the present invention;

FIG. 7 illustrates a close-up view of exemplary monolithic consumableconversion media, in accordance with exemplary embodiments of thepresent invention;

FIGS. 8A-8C illustrate exemplary NO₂—NO reactor cartridges withintegrated sensor probes, in accordance with exemplary embodiments ofthe present invention;

FIG. 9 illustrates an exemplary NO₂—NO reactor cartridge with integratedsensor probes, in accordance with exemplary embodiments of the presentinvention;

FIG. 10 illustrates an exemplary NO₂—NO reactor cartridge withintegrated sensor probes, in accordance with exemplary embodiments ofthe present invention;

FIG. 11 illustrates an exemplary NO₂—NO reactor cartridge with aspectrophotometric sensor probe, in accordance with exemplaryembodiments of the present invention;

FIG. 12 illustrates an exemplary NO₂—NO reactor cartridge with a window,in accordance with exemplary embodiments of the present invention;

FIG. 13 illustrates an exemplary NO₂—NO reactor cartridge with a windowand a spectrophotometric sensor probe, in accordance with exemplaryembodiments of the present invention;

FIG. 14 illustrates an exemplary inhalation therapy system with computercontrolled gas delivery, in accordance with exemplary embodiments of thepresent invention; and

FIG. 15 illustrates an exemplary NO₂—NO reactor cartridge with a gaschromatograph sensor probe, in accordance with exemplary embodiments ofthe present invention.

DETAILED DESCRIPTION

The principles and embodiments of the present invention relate tomethods and systems for safely providing NO to a recipient forinhalation therapy. As described above, there are many potential safetyissues that may arise from using a reactor cartridge that converts NO₂to NO, including exhaustion of consumable reactants of the cartridgereactor. Accordingly, various embodiments of the present inventionprovide systems and methods of determining the remaining useful life ofa NO₂-to-NO reactor cartridge and/or a break-through of NO₂, andproviding an indication of the remaining useful life and/orbreak-through.

In embodiments of the present invention, the chemical and physicalcharacteristics of the cartridge reactor and consumable reactants can bemeasured by suitable techniques including but not limited to volumetricand mass flow rates through the cartridge, spectroscopic analysis ofconsumable reactants, inert products, and/or gases, sampling andchromatography of gases, wet chemical analysis and/or quantitativedetection of consumable reactants and/or gases, electrochemical analysisby voltammetry and/or amperometry, and/or quantitative detection ofconsumable reactants by color change.

In embodiments, meters can detect and/or measure various characteristicsof the conversion reactor and/or gas streams, including but not limitedto the concentration of ascorbic acid, the concentration ofdehydroascorbic acid, the concentration of water (H₂O), theconcentration of NO₂, the concentration of NO, the concentration of O₂,the concentration of HNO₃, the pH of at least a portion of theconversion reactor, the redox potentials of chemical species in theconversion reactor, the mass flow rate of gases, the conductance at thesurface of the silica gel, and the humidity of incoming and outgoinggases.

Various embodiments of the present invention can be used, modified,and/or be affiliated with various systems for delivering apharmaceutical gas to a patient receiving inhalation therapy. Thesesystems can include, but are not limited to, ventilators, CPAP/BiPAP andAPAP systems, pulsed delivery systems, breathing circuits, nasalcannulas, breathing masks, and/or any other system for delivering apharmaceutical gas to a patient receiving inhalation therapy.

Generally speaking, to provide NO inhalation therapy to patient in needthereof, these systems can include, but are not limited to, a source ofgas that can provide NO as a final product, a source of air flow, asource of oxygen, a conduit that contains and/or communicates the gasand air flow to a NO₂-to-NO reactor cartridge, a delivery conduit thatcontains and communicates the NO gas and air mixture from the conversionreactor to a recipient interface.

Referring to FIGS. 1A-1B, exemplary NO delivery systems are illustrated.As shown, system 1 includes a source of gas 10, which may be a NO₂ gassource that can be connected to and in fluid communication with gassource conduit 40 that can contain and direct the gas from the source toa conversion reactor 100 and/or humidifier 45. An air supply 20, whichmay be an air pump, compressor, or wall air, may be connected to and influid communication with the gas source conduit 40 to provide a flow ofambient air with the NO₂ source gas. An optional supply of oxygen 30 mayalso be connected to and in fluid communication with the source conduit40, for example, to supplement the amount of oxygen being fed throughthe conduit(s). The source conduit 40 can be connected to and in fluidcommunication with the conversion reactor 100, which in turn can beconnected to and in fluid communication with a gas delivery conduit 50that contains and directs the gas from the conversion reactor to apatient 90. In embodiments, an NO gas source (not shown) may beconnected to and in fluid communication with the source conduit 40,alone or in combination with the NO₂ gas source.

Principles and embodiments of the present invention also relate toproviding protective elements operatively associated with a source ofNO₂, and/or a reactor cartridge, which may include components to absorbany NO₂ that may leak out of the NO₂ source and/or reactor cartridge,and color agents that indicate the presence of NO₂. In embodiments ofthe invention, the NO₂ may be absorbed by absorbents, including silicagel, alumina, soda lime, and magnesium sulfate. In embodiments of theinvention, the presence of NO₂ may be indicated by sulfanilic acid(diazotizing agent) in combination with N(1-naphthyl)ethylene diaminedihydrochloride, metalloporphyrins, for example(5,10,15,20-tetrraphenylporphyrin)-zinc, ethyl violet, and malachitegreen.

In various embodiments, a source of NO₂ gas may be encased within anouter housing that surrounds the container holding the NO₂ sourcematerial (e.g., NO₂ gas, N₂O₄ liquid, and NO gas which may react toproduce NO₂). The NO₂ container and/or outer housing may be glass,quartz, silica, steel, stainless steel, chemically resistant alloys(Waspaloy®), fluoro-polymers (e.g., Teflon®), and combinations thereof(e.g., glass or fluoro-polymer lined stainless steel). In embodiments ofthe invention, the outer housing can be large enough to encapsulate theNO₂ source container or a reactor cartridge to reduce or prevent any NO₂gas from reaching the atmosphere, and form an internal volume betweenthe inside of the outer housing and the NO₂ source containersufficiently large to hold enough absorbent to react with all of thepossibly released from the NO₂ source container. Reaction between theNO₂ gas and absorbent should be complete, such that none of the NO₂remains after interacting with the absorbent. A surplus of absorbent maybe included to provide a safety factor to ensure all of the NO₂ isabsorbed and/or reacted.

In embodiments of the present invention, the absorbents may be treatedand/or intermixed with the color agents, so that a color change of thecolor agent occurs when the absorbent interacts with the NO₂ or when atleast a portion of the absorbent is used up. In embodiments, the coloragent may be sulfanilic acid (diazotizing agent) in combination withN(1-naphthyl)ethylene diamine dihydrochloride, metalloporphyrins, forexample (5,10,15,20-tetrraphenylporphyrin)-zinc, ethyl violet, andmalachite green. In a non-limiting example, in the absence of NO₂sulfanilic acid (diazotizing agent) in combination withN(1-naphthyl)ethylene diamine dihydrochloride has white color but yieldslight purple color at about 3.7 ppm and medium purple at about 10 ppm ofNO₂. In a non-limiting example, metalloporphyrins may change from purpleto yellow. In embodiments, the color agent may also indicate changes inpH that occurs upon exposure to NO₂.

In embodiments, the outer housing may be transparent (e.g., glass,quartz, fused quartz) or have an opening in the non-transparent materialbody (e.g., steel) with a transparent window (e.g., glass, quartz, fusedquartz), so that a user may observe any color change by the color changeagent

In embodiments of the invention, the NO₂-to-NO reactor cartridge, alsoreferred to as a conversion reactor or conversion cartridge, can includean outer reactor shell or body, an inlet, an outlet, and a consumableconversion media including solid packing material coated with consumablereactant, for example an antioxidant and water, where the solid packingmaterial can be retained within the internal volume of the reactorshell, and where the coated packing material provides a consumablereactant surface. The solid packing material and consumable reactantcoating form a consumable conversion media. In one or more embodiments,the antioxidant is ascorbic acid, which can be applied to the packingmaterial in an aqueous solution, and the packing material may be silicagel. Other antioxidants include suitable reducing agents for theconversion of NO₂ to NO, such as alpha tocopherol and gamma tocopherol.Other packing material may include calcium sulfate dehydrate, calciumfluorophosphate dihydrate, zirconium (IV) oxide, zircon, titaniumdioxide, and aluminum silicate, or any suitable material that can becoated with consumable reactant and/or that can be hydrated.

In embodiments of the present invention, the agents for the conversionof NO₂ to NO also may be toluidine, benzidine, and benzidinederivatives, as presented in U.S. Pat. No. 3,106,458 issued on Oct. 8,1963, to Grosskopf et al., and incorporated herein by reference in itsentirety. The benzidine may be for exampleN,N,N,N′-tetraphenylbenzidine, N,N′-dimethyl-N,N′ diphenylbenzidine, orN,N′ diphenylbenzidine, which may be combined with a strong acid on acarrier, such as silica gel, as a reagent for NO₂. The toluidine,benzidine, and benzidine derivatives may be deposited onto the carrierand exposed to NO₂, and the toluidine, benzidine, and benzidinederivatives undergo a color change upon such exposure. In embodimentsthe reaction between NO₂ and the aromatic amines produces NO and areactant product. For example, the N,N′ diphenylbenzidine can react withNO₂ to produce NO, H₂O, and NN-diphenyl-1,4-phenylenediamine.

Referring to FIGS. 2A-2C, a general example of a packed-type NO₂-to-NOreactor cartridge 100 is illustrated. The conversion reactor has a bodywith an annular wall 110, an inlet end wall 120 that seals the inlet endof the reactor, and an outlet end wall 130 that seals the outlet end ofthe reactor to form an internal volume 150 within the reactor 100. Thereactor also has an inlet 140 that facilitates connection of the reactor100 to a gas conduit (not shown) and allows passage of gas through theinlet end wall 120 to the internal volume 150. An outlet 190 facilitatesconnection of the reactor 100 to another gas conduit (not shown) andallows passage of gas through the outlet end wall 130 to be delivered toa recipient. At least a portion of the internal volume 150 of thereactor 100 may contain a consumable conversion media 160 thatfacilitates conversion of an incoming NO₂ gas delivered to the inlet 140to an outgoing NO gas exiting at the outlet 190.

Referring to FIGS. 3A-3C, a general example of porous solid-typeNO₂-to-NO reactor cartridge 100 is illustrated. Differing from the abovedescribed packed-type NO₂-to-NO reactor cartridge, the consumableconversion media for the porous solid-type NO₂-to-NO reactor cartridge100 is a coated porous, bonded or sintered structure, for example aglass frit or sintered silica gel, in the form of a cylindrical wall 170to provide a surface area for coating with the consumable reactant, forexample ascorbic acid and water. An example of a sintered silica gel isdescribed in U.S. Pat. No. 3,397,153 A issued Aug. 13, 1968, to Sippelet al., and incorporated herein by reference in its entirety.

Still referring to FIGS. 3A-3C, a first end of the cylindrical wall 170may be capped with an end wall 172 of similar porous material or closedoff with a non-porous disk. The second end of the cylindrical wallopposite the first end may be affixed to the outlet end wall 130, suchthat the cylindrical wall 170 surrounds the outlet 190. Gas entering theconversion reactor 100 through the inlet 140 enters the internal volume150 of the reactor body including the gap 175 between the annular wall110 and the porous cylindrical wall 170, and is forced through theporous cylindrical wall 170 under pressure. The porous cylinder wall 170is affixed to the outlet end wall 130 in a manner that prevents gas frompenetrating between the cylindrical wall and end wall, as would be knownin the art of bonding technology, so all of the gas exiting the cylinderhas to pass through the porous cylindrical wall 170. A porouscylindrical wall coated with consumable reactants forms a monolithicconsumable conversion media in contrast to a packed consumableconversion media, wherein monolithic refers to a structure having adefined shape and determinable dimensions in contrast to a packedmaterial formed by a large number of separate particles that flow if notretained within a volume.

Although reference has been made to a cylindrical wall, other shapesincluding but not limited to oval, elliptical, quadrilateral, polygonal,are also contemplated and intended to fall within the scope of theinvention.

In various embodiments, the consumable conversion media, therefore, canbe a cylindrical wall or a packed bed coated with the consumablereactants. The reactant gas (e.g., NO₂), may become absorbed onto thecoated surface (e.g., silica gel) and interact with the consumablereactants (e.g., ascorbic acid and water) to produce a product gas(e.g., NO), which desorbs from the surface of the consumable conversionmedia and is transported out of the conversion reactor by a carrier gas,which may be non-reactive (e.g., N₂), reactive (e.g., O₂, H₂O), or acombination thereof (e.g., air).

It will be understood that the cross-sectional shape of NO₂-to-NOreactor cartridges, and elements thereof, can be any reasonablecross-sectional shape such as, but not limited to, round, ovoid,quadrilateral, and polygonal, to name a few. For ease, thecross-sectional shape of NO₂-to-NO reactor cartridges, and elementsthereof, is described as being round, or variations thereof. This ismerely for ease and is in no way meant to be a limitation.

With an understanding of the delivery systems and NO₂-to-NO reactorcartridges, principles and embodiments of the present invention relatingto systems and methods of determining the remaining useful life of aNO₂-to-NO reactor cartridge and/or a break-through of NO₂, and providingan indication of the remaining useful life and/or break-through can nowbe shown, for example, in greater detail. It will be understood thatvarious embodiments can be used, modified, and/or be affiliated withsystems for NO inhalation therapy that can include an initial source ofgas that is NO and/or NO₂.

In exemplary embodiments, the remaining useful life of NO₂-to-NO reactorcartridge can be determined and/or provided to users in one or moremeters, such as dosage meters. In exemplary embodiments, meters can beintegral with and/or operatively associated with a NO₂-to-NO reactorcartridge.

In exemplary embodiments, meters can include and/or be operativelyassociated with one or more sensors, which in turn may be operativelyassociated with at least a portion of the conversion reactor. Sensor canbe, but is not limited to, a flow sensor, a spectrophotometric sensor, achemical sensor, an electrochemical sensor, a pH sensor, a moisturesensor, or a combination of one or more sensors.

The meter can be internal to the reactor or external to the reactordepending upon the particular capabilities and requirements of themonitoring method. In some embodiments, the methods of monitoring aperformance characteristic require a device in contact with the gas, theconsumable conversion media, or the reactor body, for example,electrochemical monitoring. In other embodiments, the method ofmonitoring the performance characteristics may allow remote detection ofphysical or chemical property or attribute, for example,spectrophotometric analysis such as UV/VIS or FTIR analysis. In variousembodiments, an electronic signal generated by the meter can becommunicated over a communication path to a microprocessor-based systemto interpret the signal as a representative value.

The microprocessor-based system also referred to as a computer, can be asingle board computer, a laptop computer, a desktop computer, a server,a mainframe, a pad, a tablet, an application specific integrated circuit(ASIC), or other analog and digital electronic circuitry known in theart. The microprocessor-based system may be configured to receive theelectronic signals and perform data acquisition, which may be used forsubsequent calculations and determinations. A microprocessor-basedsystem may comprise transitory and non-transitory memory for storingprograms, acquired data, and calculated values as would be known in theart. The microprocessor-based system may be configured to communicateand interact with the various meters, spectrometers, and devicesdescribed herein.

Principles and embodiments of the present invention also relate todetermining the activity of the consumable conversion media, theconcentration of various components in the gas stream at variouslocations in the system, or both. Consumable conversion media componentsof interest can include ascorbic acid, dehydroascorbic acid, nitricacid, water, or combinations thereof. Gasses of interest can includeNO₂, NO, and O₂, or combinations thereof.

Principles and embodiments of the present invention also relate toidentifying sample points located within a reactor cartridge and/or aninhalation therapy system consisting of at least one reactor cartridge,and placing one or more sensor probes into the reactor cartridge and/orinhalation system, wherein one or more sensor probes may be placed ateach of the one or more sample points to monitor the various reactantsemployed in the system. Sensor probes located at sample points mayprovide particular, relevant information about the concentration ofconsumable reactants, gaseous reactants, gaseous products and anycombination thereof. The sensor probes may be connected to meters,spectrometers, and other devices through wires and/or wirelessly (e.g.,RF, optical, blue tooth, etc.) and connectors as known in the art.

In embodiments, a sensor probe may be suitably configured and adapted toperform any of the chemical and physical measurements described herein,for example, a spectrophotometric sensor probe (e.g., an optical fiber,a window), fluorescence probe, an electrochemical sensor probe (e.g.,carbon nanotube), a pH sensor probe (e.g., a micro pH electrode), achromatography sample probe (e.g., a glass or plastic cannula), or atemperature sample probe (e.g., thermistor, thermocouple), and may beprovided within a conversion cartridge or inhalation system. A sensorprobe may be combined with a suitable chemical reactant (e.g.,color-active agent, a sensitizing reagent, chemical indicator) tofacilitate or increase sensitivity of the analytical method to the otherreactants of interest.

The sensor probe(s) in combination with a suitable operativelyassociated meter and/or suitable chemical reactant is a means formonitoring the functioning of the conversion reactor and determining alifetime. The sensor probe(s) provide a means for chemically and/orphysically sampling the conversion reactor, and include an opticalfiber, a window, a carbon nanotube, a micro pH electrode, a cannula, athermistor, a thermocouple, alone or in combination with a color-activeagent, a sensitizing reagent, a chemical indicator.

The meter, including spectrometers, gas chromatographs, voltmeters,ammeters, pH meters, and flow meters, provides a means of measuring thephysical and/or chemical characteristic(s) sampled by a sensor probeand/or chemical reactant from the conversion reactor, and generatingvalues of the physical and/or chemical characteristic(s) that indicatethe level of functioning of at least a portion of the conversionreactor.

In embodiments of the present invention, sample points can be identifiedat various locations along the axial length of the NO₂-to-NO reactorcartridge, which can be quantitatively associated with the conversionreactors NO₂-to-NO performance, as well as the depletion of theconsumable reactants, such as ascorbic acid and/or water, and theaccumulation of the consumable reactant inactive materials, such asdehydroascorbic acid and nitric acid. As the consumable reactants on thepacking material are used up, the reactant gases can expect toexperience a reduced amount of surface area within the conversionreactor capable of converting NO₂ to NO. Calibrations relating theconcentration to performance can be accomplished through reactorsampling and statistical analysis, as would be known in the art ofmanufacturing and quality control. In exemplary embodiments, measurementof relative concentration of ascorbic acid and/or dehydroascorbic acid,and/or water, on the silica gel surface along the longitudinal gas flowpath can be an indication of reactor life time and/or performance.

In embodiments of the invention, locations within the conversion reactorthat can provide specific information relating to the functioning of theconsumable conversion media and consumable reactant activity of thereactor can be identified. These locations may be positioned along thelength of the reactor and/or packing material in reference to thedirection of gas flow, such that a sensor positioned at the entrylocation is positioned at a leading edge of consumable conversion mediaclosest to the inlet of the conversion reactor, and is therefore thefirst sensor to detect incoming gas or reaction products of an incominggas. A sensor positioned at the outlet location is positioned at atrailing edge of consumable conversion media closest to the outlet ofthe conversion reactor, and is therefore the last sensor to detectincoming gas or reaction products of an incoming gas.

In embodiments, there will generally be longitudinal gas flow along theaxis of the conversion reactor from an inlet to an outlet, and there maybe radial flow away from an inlet and/or reactor axis towards the wallsof the conversion reactor, as would be known in the art.

FIG. 4 illustrates a non-limiting example of a plurality of sensorprobes 201 that may be positioned within the internal volume 150 of aconversion reactor 100, and may be operatively associated with theconsumable conversion media 160, inlet 140, and/or outlet 190 of thereactor 100. In the example, the locations can include an entry samplepoint 210 located at the front end of the packing material, which may beat a leading edge of consumable conversion media 160 closest to theinlet 140, an exit sample point 280 located at the back end opposite thefront end of the packing material, which may be at a trailing edge ofconsumable conversion media 160 closest to the outlet 190, a mid samplepoint 220 half way between the front end and back end of the packingmaterial. The locations can include for example one or more intermittentsample points 240 located at various distances between the front end andback end of the reactor, where such intermittent sample points may havefixed or varying distances between them along the axis of the reactor.The sensor locations can also include a cautionary sample point 250positioned a predetermined axial distance from the trailing edge ofconsumable conversion media, that is determined by the mean free path ofa gas molecule traveling through the consumable conversion media.

In exemplary embodiments, the distance from the trailing edge ofconsumable conversion media 160 can be determined from the statisticalnumber or percentage of unreacted gas molecules (e.g., NO₂) that wouldtraverse the distance without conversion to a product molecule (e.g.,NO), where the number may be set at an absolute concentration such as0.1 ppm NO₂, or a percentage may be set at a relative amount such as 1%of NO₂ entering the reactor. Additional sensor locations may bepositioned at other sample points of interest, such as along theperiphery of the packed material to detect channeling, buried todifferent depths within the consumable conversion media to detectconversion fronts, and/or at the gas inlet or gas outlet to detect gasconcentration(s) before or after interaction with the consumableconversion media.

FIG. 5 illustrates a perspective view of a conversion reactor 100indicating the intended direction of gas flow through the internalvolume 150 and packed consumable conversion media 160. In the embodimentillustrated in FIG. 5, the packing material may be held within a portionof the internal volume by a front end retainer 155 positioned nearer theinlet 140 and a back end retainer 165 opposite the front end retainer155 and positioned nearer to the outlet 190 of the reactor. There may bea gap between the inlet end wall 120 and the front end retainer 155 thatdoes not contain any packing material and forms an open internal volumeat the inlet 140. There may also be a gap between the outlet end wall130 and back end retainer 165 that does not contain any packing materialand forms an open internal volume at the outlet 190.

In the non-limiting example illustrated in FIG. 5, the sample probes 201are buried within the consumable conversion media 160 to a predetermineddepth, so that the probes may not be in contact with the annular wall110 of the reactor. In the illustrated embodiment, a plurality of sensorprobes 201, for example six (6), are arranged in a hexagonal pattern anequal distance from the front end retainer 155. An additional set of sixprobes 201 arranged in a second hexagonal pattern may be located anequal distance from the probes located closest to the front end retainer155. Similarly, a third set of probes 201 arranged in a third hexagonalpattern may be located an equal distance from the second set of probes,as may additional fourth, fifth, etc., sets of probes. Each set ofprobes may be arranged in the same radial plane, which can beperpendicular to the reactor axis and intended axial gas flow.

FIG. 6 illustrates a perspective view of a conversion reactor 100indicating the intended direction of gas flow through the internalvolume 150 and cylindrical wall 170 of the monolithic consumableconversion media. The gas enters through the inlet 140 and passesthrough the internal volume 150 and gap 175 to the monolithic consumableconversion media, which can be semi-permeable. The gas passes throughthe porous cylindrical wall 170 of the semi-permeable, monolithic,consumable conversion media into the hollow space 180 and out throughthe outlet 190. NO₂ gas passing through a consumable reactant coatedcylindrical wall 170 can be converted into NO through interaction withconsumable reactants (e.g., ascorbic acid and H₂O) on the surfaces. Inexemplary embodiments, the thickness of the cylindrical wall should begreater than the mean free path of the gas through the porous wallmaterial to ensure all of the NO₂ interacts with a consumable reactantcoated surface before reaching the hollow space 180.

While the direction of gas flow has been illustrated as from theexterior of the semi-permeable wall 170 into the interior hollow space180, in embodiments the direction may be reversed without departing fromthe spirit and scope of the invention.

A close-up view of a porous cylindrical wall 170 with an end coveredwith the same porous material is illustrated FIG. 7, which shows athickness T1 of the cylindrical wall 170, a thickness T2 of the endcover, and a thickness T3 at a corner formed by the cylindrical wall andend cover. Where the relationships between the thicknesses are T3>T1,T3>T2, and T1 can be greater, equal, or less than T2. Gas passing fromone side of the cylinder to the other travels a distance D through theporous material, where D is greater than or equal to the smallestthickness. In embodiments in which the porous cylindrical wall is coatedwith a consumable reactant(s) (e.g., ascorbic acid, H₂O) and exposed toa reactant gas (e.g., NO₂), the consumable reactant is used up overtime.

Also as illustrated in FIG. 7, the ongoing flow of reactant gas throughthe coated walls generates a conversion front 310 in which the reactantcomponents have been essentially depleted (e.g., consumed) on one sideof the front and are still sufficiently active on the other side of thefront. In the non-limiting example, the conversion front will advancethrough the consumable conversion media as more and more of the reactantcomponents are exhausted, until the reactant gas, NO₂, begins to passthrough the wall(s) without conversion to the product gas, NO. Theconversion front may advance a distance into the wall thickness T1 andT2 by time t1, and a greater distance by time t2, such that the NO₂passes through the porous cylindrical wall without conversion to NO atone or more points around the cylindrical wall 170 and end wall 172.

In embodiments of the invention, the total area of the cylindrical wall170 and end wall 172, calculated as A=2πrh+2πr2, where h is the lengthof the cylindrical wall and r is the radius of the cylindrical wall, isgreater than the circular area of a front face of packed consumableconversion media 160, so the possible location of a channel in thecylindrical wall is greater. The number of probes required to detectchanneling may therefore be greater for the cylindrical wall consumableconversion media 170 than for a packed consumable conversion media 160.

In embodiments illustrated in FIG. 8A, sensor probes 201 may be placedalong the internal side of the cylindrical wall 170 to monitor theconsumable conversion media components of interest. The sensor probes201 may be embedded within the cylindrical wall or affixed to theinternal surface of the cylindrical wall 170, or both. The sensor probesmay monitor the consumable conversion media components of interestand/or the gases of interest, and communicate electric signals to anelectric circuit (i.e., meter) that measures the amounts detected andmay communicate the amounts to a computer as an electrical signal forcomparison with established threshold values.

In embodiments illustrated in FIG. 8B, sensor probes 201 may be placedin a row within the cylindrical wall 170, wherein the sensor probes maybe arranged as a linear array along at least a portion of the length ofthe cylindrical wall 170. An axial array may be placed on one or moresides of the cylindrical wall 170 to determine if the consumableconversion media is being depleted evenly on different sides of thecylindrical wall 170. As a non-limiting example, the sensor probes maybe single-wall carbon nanotubes with manganese-porphyrin, which may benitrogen dioxide selective sensors based on amperometric changes asdisclosed in Popescu M et al. Sensor of Nitrogen Dioxide Based on SingleWall Carbon Nanotubes and Manganese-Porphyrin. Digest Journal ofNanomaterials and Biostructures Vol. 6, No 3, July-September 2011, p.1253-1256, incorporated herein by reference in its entirety.

In embodiments, sensor probes 201 may be placed around the circumferenceof the cylindrical wall 170, where the sensor probes form a circulararray.

In embodiments illustrated in FIG. 8C, the probes 201 may be placedradially within the cylindrical wall 170, where one or more sensorprobes are placed at different distances from the exterior surface ofthe cylindrical wall 170 to determine if the gases are passing uniformlythrough the wall thickness.

FIG. 9 illustrates a hypothetical flow of gas from the inlet 140 throughthe consumable conversion media 160 held in place by a front endretainer 155 and back end retainer 165. As illustrated in the example,source gas, for example NO₂, may enter the inlet 140 at an initial timezero t0, and advance through the consumable conversion media, where theNO₂ interacts with the consumable conversion media. The consumableconversion media becomes exhausted by the reaction with the incominggas, such that NO₂ entering the consumable conversion media 160 passesthrough a detectable distance by some later time t1, without conversionto the product gas, for example NO. The exhaustion of the consumableconversion media or presence of a gas of interest may be detected by aset of sensor probes 201 located at the first distance from the frontend retainer 155 (also shown in FIG. 5).

In the illustrated example, the sensor probes 201 at the conversionfront indicate when the consumable conversion media between the frontend retainer 155 and first arrangement of probes 201 is no longeractive. Similarly, at some later time t2, the second arrangement ofprobes 201 indicate that the NO₂-to-NO conversion front has advanced theadditional distance between the first and second sets of sensor probes201, and again for an even later time t3. At an even later time t4, themajority of consumable conversion media has been used up and at least aportion of the NO₂ entering the inlet can pass through the consumableconversion media 160 and exit the reactor unconverted. This passage ofat least a portion of the entering NO₂ through the conversion reactorunconverted to NO is referred to as break-through. The length of thepacked region of the reactor that becomes unreactive at the time ofinitial break-through can be determined experimentally and/ortheoretically, and an arrangement of sensor probes can be positioned thedetermined length from the front end retainer 155 or back end retainer165 to detect when break-through is imminent to protect a recipient froma toxic dose of NO₂.

As can be appreciated, reliance on experimental and theoreticalinformation (e.g., average life-time, calculated points ofbreak-through) can fail to account for real-life deviations from ahypothetical expected or optimum performance. It can be extremelydifficult to account for all the potential failure modes of a consumablecartridge, some of which are presented in at least the various exemplaryscenarios described herein, using high level averages and broad modelingassumptions. Importantly, appropriately located sensor probes can beused to determine actual reactor cartridge lifetime by taking real-timemeasurements, which can take manufacturing and performance deviationsdirectly into account, and/or provide users with lifetime information,for example, in a meter to at least increase patient safety andefficacy.

FIG. 10 illustrates an example of channeling along an outer edge ofconsumable conversion media 160 adjacent to an annular wall 110 of theconversion reactor 100. In the illustrated example, the NO₂-to-NOconversion front 310 may advance more quickly at the interface betweenthe coated packing material and annular wall 110 due to looser packingand/or settling of the packing material from vibration in transportationand handling, mechanical shock, aging and deterioration of thematerial's physical integrity. As shown in the example, the conversionfront 310 no longer propagates primarily through the bulk of theconsumable conversion media, but advances along an outside edge. In anembodiment, the sensor probes 201 can be positioned around the peripheryof the consumable conversion media 160 adjacent to the inside surface ofthe annular wall 110 to detect such channeling.

For example, a first set of four (4) sensor probes may be arranged inthe same radial plane around the periphery of the consumable conversionmedia 160 with one (1) probe located in each quadrant of the conversionreactor. The first set of four sensor probes may be located at apredetermined distance from the front end retainer 155 or the inlet endwall 120. A second set of four sensor probes may be located at apredetermined distance from the front end retainer 155 or the first setof sensor probes. Similarly, a third set of four sensor probes 201 maybe located at a predetermined distance from the front end retainer 155or the second set of sensor probes.

As shown in FIG. 10, the conversion zone 310 may advance farther in onequadrant of the consumable conversion media (e.g., the upper section)faster than in the other three quadrants, so that at time t1 the sensorprobe 201 in that quadrant detects exhaustion of the consumableconversion media even though the other three probes still indicate theconsumable reactants are active. By time t2, the conversion front 310has already propagated past the probe 201 in the upper quadrant, whilethe remaining three probes in the second set still indicate theconsumable reactant's activity. By time t3, NO₂ break-through has justoccurred in the compromised quadrant by the time the last probe in thesecond set indicates exhaustion of the consumable conversion media inthat quadrant.

In embodiments of the invention, the progression of the consumablereactant exhaustion along a particular path can be mapped to determinethat at least particular sections of the reactor may be compromised, aswell as when break-through may be expected, and provide a warning to auser that replacement of a reactor is necessary.

In various embodiments, a combination of sensor probes may be arrangedboth within the bulk and around the periphery of the consumableconversion media to monitor an expected propagation of the conversionfront and determine if channeling is occurring in the consumableconversion media.

While the above embodiments and examples referred to specific numbersand geometrical arrangements of the sensor probes, it is understood thatother quantities and arrangements of the probes are contemplated and maybe used without departing from the spirit and scope of the invention.

A sensor probe may be one or more component(s) that undergo a chemicalor physical change due to interaction with a gas of interest orconsumable conversion media component of interest, for example one ormore carbon nanotubes embedded in the consumable conversion media withelectrical wires from the nanotube(s) to an external connector on thereactor body. The sensor probes may also be a device operativelyassociated with a reactor that communicates a detectable signal from alocation within the reactor's internal volume to a measuring device(e.g., meter) remote from the reactor, for example, a fiber optic linethat receives light signals from a volume of gas or surface area andtransmits the signal to a spectrophotometer for UV/VIS/IR analysis.

It will be understood that principles and embodiments described withreference to porous solid-type NO₂-to-NO reactor cartridges, andelements thereof, and principles and embodiments described withreference to packed-type NO₂-to-NO reactor cartridge, and elementsthereof, can, when applicable, be implemented in either configuration.For example, at times, sensor probes, sample points, sensors, and thelike are described with reference to porous solid-type NO₂-to-NO reactorcartridges, and elements thereof, such as cylindrical wall, cylindricalwall consumable conversion media, consumable conversion media, etc. orare described, at times, with reference to packed-type NO₂-to-NO reactorcartridge, and elements thereof, such as packed consumable conversionmedia, consumable conversion media, etc. This is merely for ease and isin no way meant to be a limitation. Accordingly, reference made to onetype of reactor cartridge or another, at times, is made for ease and isnot meant to be limited to that type of reactor cartridge.

Principles and embodiments of the present invention relate to measuringthe color change of a reactant that chemically interacts with one ormore gas(es) of interest to determine the amount of gas present. In anembodiment, the gas of interest is NO₂, and the reagent chemicallyreacts with the NO₂ in a manner that results in a color change of thereactant. The color change may be determined visually by an observer oruser, or the color change may be detected spectrophotometrically, forexample by a device, such as a single chip spectrophotometer using microelectro-mechanical system (MEMS) technology. The extent of the colorchange can provide a quantitative determination of the amount of gaspresent in a specific volume and thereby determine a concentration. Inembodiments, a spectrometer or spectrophotometer or colorimeter canoutput an electronic signal that can be used to determine the extent ofa color change, and the signal may be communicated to a computer fordisplay or the triggering of an alarm.

The combination of a color active agent, a fiber optic or window sampleprobe, and a spectrometer or spectrophotometer or colorimeter (hereinreferred to as a spectrometer) provides a means for monitoring thefunctioning of the conversion reactor and determining a lifetime of theconversion media.

In an embodiment, the color-active agent can be located within theinternal volume at the outlet end of a conversion reactor in order todetect and signal the presence of NO₂ in the outlet gas stream.Detection of a predetermined amount of NO₂ in the outlet stream can beused to trigger a cut-off of gas delivery to a recipient.

In a non-limiting example illustrated in FIG. 11, a material segment 420can be positioned in the internal volume 150 at the outlet end of thereactor 100, where the material segment 420 may be affixed to the outletend wall 130, the back end retainer 165, the annular wall 110, or acombination thereof. The material segment 420 can be porous and coatedwith the color-active agent, and is located in the exiting gas flow, sothat gas components impinge on the surface of the coated porousmaterial. In an embodiment of the present invention, the color activeagent coated on the surface of the material segment 420 could beo-phenylenediamine or 2,6-dichlorophenolindophenol in combination withascorbic acid. When NO₂ passes through the conversion media unreacted,the NO₂ reaches the outlet end of the reactor and interacts with thecolor active agent indicating NO₂ is leaving the cartridge. A fiberoptic sensor probe 430 can be inserted into the reactor 100 through anopening in the annular wall 110 of the body, and configured to receive asignal from at least one surface of the coated porous material 410.Impinging light from a radiant source having an acceptable spectrumcould be supplied by the same fiber optic line 440 or another fiberoptic line (not shown). The fiber optic line 440 can receive lightreflected off of the color-active agent and communicate the light to aspectrometer 500 for wavelength detection and intensity measurement, forexample absorbance or fluorescence, as would be known in the art ofspectroscopic analysis. Detection of a characteristic absorbance spectradue to a sufficient color change to indicate the presence of particulargas components (e.g., NO₂) could be communicated to a computer 800 fordisplay, triggering an alarm, or both. In an embodiment, the coatedmaterial 410, spectrometer 500, and computer 800 may be configured todetect a concentration of 0.1 ppm NO₂ or greater in the gas streamexiting the conversion reactor, or a concentration of 1.0 ppm NO₂ orgreater in the gas stream.

In embodiments of the present invention, the color-active agent may beo-phenylenediamine which reacts with dehydroascorbic acid (DHAA) to forma tricyclic, highly fluorescent condensation product, the presence ofwhich can be qualitatively and quantitatively determined byspectrophotometric analysis with a spectrometer or spectrometer.

The spectrophotometer can be operatively associated with thecolor-active agent, and may be positioned locally with the agent, forexample, with a single chip spectrometer or spectrophotometer orcolorimeter mounted to the system, or remotely using a fiber optic linethat communicates a light signal from the color active agent to theremote spectrometer or spectrophotometer or colorimeter.

In embodiments of the invention, the o-phenylenediamine can function asa redox sensor to detect the presence of DHAA. The presence of DHAAindicates depletion of the consumable reactant ascorbic acid and theexhaustion of the conversion reactor.

When the reactor is configured as a packed column, incoming NO₂interacts with the consumable reactant's active consumable conversionmedia closest to the reactor inlet first. As the conversion material isused up by exposure to the NO₂, additional incoming NO₂ passes furtherinto the packed column before reaching an active surface of theconsumable reactant. This process proceeds through the packed materialuntil NO₂ can pass all the way through the reactor without interactingwith a consumable reactant surface. At this point NO₂ break-throughoccurs, and the reactor is effectively depleted.

Break-through may be when NO₂ is at a concentration of 0.1 ppm in thegas stream exiting the NO₂-to-NO reactor cartridge, or when the NO₂ isat a concentration of 1 ppm in the exiting gas stream, or the NO₂ is ata concentration of 5 ppm in the exiting gas stream.

In embodiments of the invention, small amounts of o-phenylenediamine canbe located at discrete locations along the flow path of the gasesthrough the packed material as redox sensors. As the consumableconversion media is depleted and the ascorbic acid becomes DHAA, theo-phenylenediamine reacts with the DHAA to form the florescent compound.This florescent characteristic can then be detected along the length ofthe packed column indicating how much ascorbic acid has been used up andhow much active surface remains. A physical location where break-throughis statistically possible due to the remaining flow path length of theNO₂ can be determined, and an alarm or indicator triggered to alert auser to the necessity of changing the reactor before a recipient ispoisoned by toxic levels of NO₂.

In embodiments of the invention, the determination that break-through ofthe NO₂ is imminent can be used to actuate a regulating device to haltthe delivery of at least the NO₂ gas to the recipient before poisoningoccurs. The regulating device may cut off flow of NO₂ from its source,cut off gas flow exiting the conversion reactor, divert air flow aroundthe conversion reactor to continue air/O₂ delivery to a recipientwithout NO, or divert flow of the NO₂/air mixture to an auxiliaryconversion reactor depending upon the system configuration and therapyprotocols for the recipient.

In another embodiment, the color active agent can be2,6-dichlorophenolindophenol, (DCPIP), which is a chemical compound usedas a redox dye, which when oxidized appears blue, appears pink whenoxidized in the presence of acid, or appears colorless when reduced.

DCPIP can be used as an indicator for the presence/absence of ascorbicacid (i.e., vitamin C). If ascorbic acid (AA) is present, the blue dye,which turns pink in acidic conditions, is reduced to a colorlesscompound by ascorbic acid. The absence of ascorbic acid will result inthe oxidized form of DCPIP, which is pink.DCPIP(blue)+H+→DCPIPH(pink)  [1]DCPIPH(pink)+AA→DCPIPH2(colorless)+DHAA  [2]DCPIPH2(colorless)+NO₂ or HNO₂→DCPIPH(pink)+NO+H2O  [3]

AA=ascorbic acid; DHAA=dehydroascorbic acid

Chemical reaction [1] is an acid/base reaction, while chemical reactions[2] and [3] are redox reactions. In equation [2] ascorbic acid (AA) isoxidized to dehydroascorbic acid (DHAA), and DCPIP is reduced to thecolorless compound DCPIPH2. In equation [3] the colorless compoundDCPIPH2 is oxidized to DCPIPH (pink) by the presence of NO₂ and/or HNO₂.Therefore the consumption (end point) of ascorbic acid will be indicatedwhen a permanent pink color persists.

In an embodiment of the invention, a small amount of the DCPIP dye canbe mixed evenly throughout the consumable conversion media. The initialappearance of the DCPIP will be colorless due to reduction of the DCPIPby the ascorbic acid. When all the ascorbic acid in the consumableconversion media is consumed by reaction with the continuous flow ofNO₂, there will not be sufficient electrons available to keep DCPIP inits reduced form (DCPIPH2) and the consumable conversion media will thenshow a permanent pink color due to the formation of DCPIPH.

In an embodiment of the invention, the outer reactor shell or body ofthe NO₂-to-NO reactor cartridge can further include a transparent windowthat allows the color of the consumable conversion media to bephysically observed by a user to determine when the DCPIP shows a pinkcolor or representative color change. The transparent window in the bodyof the reactor may be made of glass, quartz, or a suitable plastic, forexample polycarbonate or polyethylene terephthalate.

Principles and embodiment of the present invention also relate todetermining the amount of moisture present in the consumable conversionmedia with a color-changing compound. A chemical compound may indicate achange in moisture content of the consumable conversion media. Thechemical compound anhydrous cobalt chloride (CoCl₂) is blue, but itturns purple when it bonds with two water molecules to form CoCl₂.2H₂O.As described in the embodiments above, the CoCl₂ can be mixed evenlythroughout the consumable conversion media. The initial color would bepurple indicating that the consumable conversion media containssufficient water to support the reaction of the ascorbic acid with theNO₂. However, the compound would turn blue when the water in the reactoris used up. A user could determine the reactor was no longer functioningby observing the color change through the reactor window.

A non-limiting example of a conversion reactor 100 with a window 180made of a material transparent to the wavelengths of interest andunreactive with the gases of interest and consumable reactant materialsis shown in FIG. 12. The window may be formed in the annular wall 110 ofthe conversion reactor 100.

In another non-limiting example, illustrated in FIG. 13, a spectrometer500 may be affixed to the outside of the conversion reactor 100 andoperatively associated with the window 180 in the annular wallsurrounding the consumable conversion media. A light source or broad ornarrow spectrum may illuminate the consumable conversion media 160 andthe spectrometer 500 may detect the spectrum and/or intensity of lightreflected off of a region of consumable conversion media 160 coated witha color active agent 178, as would be known in the art. An electricalsignal may be communicated from the spectrometer 500 to a computer 800to calculate the amount of color change detected for the color activeagent 178. If the computer determines that a threshold value indicatingthat a predetermined amount of consumable conversion media component ofinterest has been reached, the computer can alert a user through adisplay, an audible alarm, or both that the reactor is exhausted orcompromised.

In a non-limiting embodiment, a spectrometer can detect the presence ofoxidized DCPIP at approximately 600 nm. An electronic signal can betransmitted from the spectrometer to a computer configured for dataacquisition and to determine when the absorbance at the 600 nmwavelength has changed by a predetermined amount. The computer can alerta user through a display, an audible alarm, or both that the reactor isexhausted or compromised.

In an embodiment, the trigger may be a signal from a spectrophotometricdevice to a microprocessor based system in electrical communication withthe spectrophotometric device, where the computer then halts the flow ofNO₂ to the recipient by sending an electrical signal to an apparatus ordevice regulating gas flow. A regulating device may be for example aventilator, a valve, a pump, a diverter, a gas tank regulator, a heatershut-off, or any other device implemented in the system to generate orcontrol a gas flow.

The regulating device, including a ventilator, a valve, a pump, adiverter, a gas tank regulator, and a heater shut-off, is a regulatingmeans for halting the delivery of the gas to a recipient. The regulatingmeans may be in electronic communication with a computer over acommunication path, and configured to receive an actuating signal fromthe computer to change the state of the regulating means from aconfiguration in which gas can flow through the regulating means to astate in which gas cannot flow through the regulating means.

In an embodiment, the gas stream exiting the conversion reactor may bepassed through a transparent tubular section containing a material thatcan change color relative to the absolute concentration of one or moregases of interest. A color change within the transparent tubular sectionmay be directly observable by a user, or the color change may bedetected spectrophotometrically, which communicates a signal to areadout, triggers an alarm, or actuates a flow regulation device.

In embodiments a sample of gas exiting the conversion reactor may bediverted from the delivery conduit into a side stream. The side streamof gases may be passed through the transparent tubular sectioncontaining the material that changes color, introduced into aspectrophotometer, a mass spectrometer (e.g. for determining theconcentration of gases, etc.), or reaction vessels that produce a knownchemical response to the gases of interest.

Principles and embodiments of the invention relate to detectingcomponents in the gas mixture or on the consumable reactant surfacedirectly using ultraviolet (UV), visible (VIS), or infrared (IR)spectroscopy.

In an embodiment of the invention, a fiber optic UV/VIS sensor can bepositioned to detect chemical concentration at a point in the consumableconversion media along the path length of the gas flow. The UV/VISSpectra obtained in real time from the consumable conversion media canindicate the relative amounts of ascorbic acid, dehydroascorbic acid,and nitric acid by measuring the absorbance at a suitable wavelength,for example 320 nm, 295 nm, and/or 265 nm.

In an embodiment, the Beer-Lambert Law may be applied; where, forexample, a decrease in ascorbic acid on the packing material may bedetermined and monitored by taking repetitive measurements atapproximately 265 nm. In an embodiment, an increase in dehydroascorbicacid may be determined and monitored by taking repetitive measurementsat approximately 310-320 nm. In an embodiment, an increase in nitricacid ion may be determined and monitored by taking repetitivemeasurements at approximately 220 nm.

In an embodiment, one or more fiber optic probe(s) may be insertedthrough the annular wall of the conversion reactor, such that the probecan detect changes in the ascorbic acid, dehydroascorbic acid, nitricacid, or combinations thereof, at a location along the length of thepacked reactor. A measurement of the ascorbic acid, dehydroascorbicacid, nitric acid, or combinations thereof would be indicative of theamount of consumable reactant activity remaining for the reactor, basedupon the mean-free path of gaseous NO₂, whereby a predetermined changein ascorbic acid, dehydroascorbic acid, nitric acid, or combinationsthereof indicates that the reactor has a limited conversion capacityremaining. The value of the predetermined change can be correlated withthe extent of reactor life remaining or the amount of consumableconversion media used up through suitable calibration and statisticalanalysis.

The combination of a fiber optic sensor probe and a spectrometer a meansfor monitoring the functioning of the conversion reactor and determininga lifetime of the conversion media.

In embodiments Infrared (IR) spectroscopy may be employed to detectabsorbances due to particular functional groups, including but notlimited to carbonyl, hydroxyl, olephinic (e.g., C═O, C═C, —OH), presenton a reactant or product for ascorbic acid and dehydroascorbic acid, aswould be known in the art of organic spectroscopy.

It should be understood that spectrometry may be combined as a detectionmethod with the other metering techniques discussed herein, where forexample an optical fiber may be used in conjunction with anelectrochemical probe at the same sample point to gather a combinationof different chemical information at the same time from the same point,or in conjunction with gas chromatograph sampling to detect for exampleNO₂ in an exiting gas stream.

In one or more embodiments, a sample of gas constituting a portion orpercentage of the gas by volume may be diverted from the gas conduit ordelivery conduit to a gas chromatograph that can separate and quantifythe amount of each gas of interest to determine if a clinicallyunacceptable amount of gas is present in the system. This could meantoxic levels of NO₂ or insufficient levels of NO, which could be due toinsufficient levels of consumable reactant activity in the reactor,channeling and/or breakthrough of NO₂ without conversion to NO, or otherfailures of the system.

In embodiments, one or more cannula sensor probe(s) may be insertedthrough the wall of a conversion cartridge and/or into an open volume150 and/or gap 175, within the cartridge to obtain samples of the gasespresent at the one or more sample points 210, as discussed herein. Thegas sample may be communicated through a sample tube to the injector ofa gas chromatograph for analysis.

The combination of a cannula sensor probe and a gas chromatographprovides a means for monitoring the functioning of the conversionreactor and determining a lifetime of the conversion media.

In embodiments, the REDOX reactions involved in converting NO₂ into NOby interaction with ascorbic acid and water on a silica surface can bedetected by measuring changes in electrical potential generated bychanges in concentration of the different chemical species of interest.For example the pH of an active surface area of consumable conversionmedia having ascorbic acid (I) is lower than surface area of consumableconversion media having dehydroascorbic acid (II), where dehydroascorbicis the oxidized form of ascorbic acid and is more basic. Ascorbic acidhas a reduction potential of 0.127 V, and pKa's of 4.17 and 11.57, whichcan be measured.

In an embodiment, a series of sensor probes, which can bemicro-electrochemical sensors along the reactor's axial gas flow path,can detect changes in the oxidation/reduction potentials as ascorbicacid is converted into dehydroascorbic acid through reaction with NO₂.Since the oxidation potential of ascorbic acid changes with the pH, andthe pH changes with ratio of ascorbic acid to dehydroascorbic acid, therelationship of concentration-to-pH-to-redox potential can bedetermined. When the potential measurement reaches a value indicative ofpredominately dehydroascorbic acid on the consumable conversion media,an electric circuit (e.g., meter) can generate a signal that can becommunicated to a computer and/or produces a readout or triggers analarm.

The combination of an electrochemical sensor probe and voltmeter and/orammeter provides a means for monitoring the functioning of theconversion reactor and determining a lifetime of the conversion media.

In an embodiment, the reduction potential for NO of about −0.8V can bedetected by one or more micro-electrochemical sensors along thereactor's axial gas flow path.

In an embodiment, the voltammetric behavior of ascorbic acid and/ordehydroascorbic acid at a glassy carbon electrode may be measured whensubjected to ultrasound. Ultrasonically formed radicals may be detecteddue to changes in an anodic signal during a sweep voltammogram, asdisclosed in Electroanalysis, Vol. 8, Iss. 3, pages 218-222, March 1996,incorporated herein by reference in its entirety.

In an embodiment, the sensor probes can be micro pH sensors that candetect changes in pH due to the conversion of ascorbic acid todehydroascorbic acid. Micro pH sensors can have a 1 mm or sub-1 mmdetection tip that can be inserted through a suitable opening in theannular wall of the conversion reactor configured and dimensioned toreceive the pH sensor. The sensor can be electrically connected to anelectric circuit (e.g., pH meter) that detects changes in pH, as isknown in the art, and may communicate an electric signal to a computerfor display and/or triggering an alarm.

The combination of a pH sensor probe and pH meter provides a means formonitoring the functioning of the conversion reactor and determining alifetime of the conversion media.

In an embodiment, the sensor probes may be micro-conductivity sensorsthat can detect changes in the conductivity of the media surface due toreduced amount of water on the surface and/or differences inconductivity between the ascorbic acid and dehydroascorbic acid on thesurface.

The combination of a conductivity sensor probe and voltmeter and/orammeter provides a means for monitoring the functioning of theconversion reactor and determining a lifetime of the conversion media.

In an embodiment, the sensor probes may be magnetic probes sensors thatcan detect changes in the conductivity of the media surface due toreduced amount of water on the surface and/or differences inconductivity between the ascorbic acid and dehydroascorbic acid on thesurface.

The combination of a magnetic sensor probe and voltmeter and/or ammeterprovides a means for monitoring the functioning of the conversionreactor and determining a lifetime of the conversion media.

In embodiments, a plurality of sensors can be arrayed both axially andcircumferentially, so that multiple rows of sensors are arranged 180°,120°, 90°, or 45° apart and sensors in each row are separated by auniform distance along the length of the consumable conversion media, asdepicted in FIGS. 5, 9, and 10. The evenly spaced axial andcircumferential sensors can detect a depletion front propagating fromthe inlet, where NO₂ enters the reactor, to the outlet, where NO shouldexit the reactor, as each circumferential ring of sensors detects theconversion of the ascorbic acid to dehydroascorbic acid. The axial andcircumferential sensors may also detect channeling through theconsumable conversion media, as particular axial sensors detectconversion and deactivation of the media before other sensors around thesame circumferential ring. For example, a particular axial row ofsensors may detect pH values or reduction potential values indicatingdepletion of the ascorbic acid along a particular axial path of thereactor before other rows of sensors detect equivalent values, therebyindicating axial channeling of the NO₂ flow along a side of the reactor.

In an embodiment, the sensor(s) can be embedded into the consumableconversion media of the packed reactor along the reaction path, therebyproviding an electrochemical map of the reaction zone.

In an embodiment, voltages and/or currents can be detected usingsuitable electronics, as would be known to those of ordinary skill inthe art, and an electronic signal may be sent to a computer to generatea readout, a visual depiction of the sensor array and readings, and/ortrigger an alarm if depletion or breakthrough is imminent. Reactordepletion may be determined by a majority of circumferential sensorslocated approximately equal distant from the reactor outlet showingconsumable reactant inactivity, whereas break through may be determinedby an axial string of sensors including at least one closest to theoutlet showing consumable reactant inactivity.

Principles and embodiments of the present invention relate to a methodof detecting channeling of gas flow through a packed conversion reactorby detecting pH values and/or redox potentials at a plurality of pHand/or redox sensors arranged in an annular array around the peripheryof a cylindrical volume of consumable conversion media.

In an embodiment of the present invention, an array of pH and/or redoxsensors can determine when a gas of interest will break through to theoutlet of a conversion reactor by detecting a threshold value for atleast one sensor located closest axially to the outlet.

As each sensor in an array indicates consumable reactant inactivity dueto conversion to dehydroascorbic acid, it would indicate that aparticular volume of consumable conversion media surrounding the sensorhas been depleted or compromised.

In an embodiment of the present invention, a meter may be placed at thedistal end of the conversion reactor outlet to detect one or more gassesof interest exiting the reactor, in particular, an NO₂ sensor probe maybe located in the delivery conduit connected to the outlet to measurethe amount of NO₂ leaving the conversion reactor. The sensor probe maybe a chemical or electrochemical sensor that reacts with the exiting NO₂and converts it to another chemical species, thereby removing thedetected amount of NO₂ from the delivery gas stream flowing to arecipient.

Principles and embodiments of the present invention also relate todetecting conversion media components of interest by electrogeneratedchemiluminescence (ECL), for example by detecting the emission ofphotons at one or more electrochemical sensor probes with an opticalfibbed probe and spectrometer.

In exemplary embodiments, sensor information above can be quantified todetermine the remaining useful life of a NO₂-to-NO reactor cartridgeand/or a break-through of NO₂, and/or provide an indication of theremaining useful life and/or break-through. For example, informationfrom a plurality of sensors at discrete locations in the reactorcartridge can be considered to be indicative of the remaining usefullife at the sensor's discrete location, and may be mapped. Informationfrom discrete locations can be quantified to indicate the remaininguseful life of the reactor cartridge as a whole.

Principles and embodiments of the present invention relate todetermining the mass and/or volumetric amount of NO₂ that can beconverted to NO by a conversion reactor, applying a safety margin to thedetermined volume of NO₂, and recording the determined value for laterreference. In an embodiment, the safety factor is applied to compensatefor statistical variations in manufacturing, tolerances, and performancecharacteristics of the reactor, as well as real-world inaccuracies inmeasurements. The determined value and safety factor establishes atheoretical NO₂ break-through value at which the reactor would beconsidered depleted and requiring replacement to maintain safeoperation.

In embodiments, the amount of NO₂ passing into a characterized reactorcan be measured by an appropriate mass flow meter(s), for example a vaneflow meter, a hot wire flow meter, a membrane temperature sensor, or aKarman Vortex meter. Once the amount of NO₂ measured by the flow meterreaches the determined value of the reactor, flow of the NO₂ can behalted to prevent break-through to a recipient. In embodiments, a flowmeter can be placed between the gas source and the conversion reactor. Avalve can be placed downstream of the flow meter and before theconversion reactor. When the amount of gas passing through the flowmeter reaches the theoretical NO₂ break-through value, a computer cantrigger the valve downstream of the flow meter to close, therebyshutting off gas flow to the reactor and halting the delivery of NO/NO₂to a recipient. In embodiments, an auxiliary air/O₂ line can be providedin parallel to the conversion reactor line, so that air/O₂ may continueto flow to the recipient after the NO₂ gas source is valved off.

The flow meter and voltmeter and/or ammeter provides a means formonitoring the functioning of the conversion reactor and determining alifetime of the conversion media.

FIG. 14 illustrates an inhalation therapy system 1 having a gas source10 that can supply for example NO₂ through a source conduit 40 to a flowmeter 43. Gas exiting the flow meter can be fluidly communicated to avalve 47 and from the valve 47 to a conversion reactor 100 by the sourceconduit 40. Gas entering the conversion reactor 100 may be converted toa product gas, for example NO, and fluidly communicated from the reactorto a recipient through a delivery conduit 50. A computer 800 inelectrical communication with the flow meter 43 monitors the amount ofgas passing through the meter and can calculate the amount of NO₂ fed tothe conversion reactor based on its concentration in the gas source 10.When the computer 800 determines that the amount of NO₂ fed to theconversion reactor has reached a predetermined value established for thereactors expected life, the computer can send an electrical signal tothe valve 47 triggering it to close in order to prevent toxic NO₂ fromflowing through an exhausted conversion reactor 100 and reaching therecipient.

In an embodiment, a valve 57 may be connected to and in fluidcommunication with the delivery conduit 50 and an air supply 20, and avalve 67 may be located between the air supply 20 and gas source 10.When the computer 800 determines that the amount of NO₂ fed to theconversion reactor has reached a predetermined value established for thereactors expected life, the computer 800 can send an electrical signalto valve 57 to open at the same time that valve 47 is triggered toclose, in order to continue providing air to the recipient through thedelivery conduit without any NO₂ or product gases. A valve 67 may betriggered to close by the computer 800 to isolate the air supply 20 fromthe source gas 10, so only air is provide through alternate conduit 60.

In another embodiment, a gas source 65 supplying NO may be connected toand in fluid communication with the air supply 20 and alternate conduit60 to provide a predetermined concentration of NO to the recipient whenvalve 47 closes.

The determined value for the characterized conversion reactor can bestored in a suitable non-volatile memory device or other non-transitorycomputer readable media (e.g., 1- or 2-D bar codes) provided with orattached to the characterized reactor, or stored in the non-volatilememory of a microprocessor-based system. In an embodiment, the flowmeter may be in electronic communication with the microprocessor-basedsystem, and communicate real time measured values from a flow meter tothe microprocessor-based system for determination of the remaining lifeof the reactor and the occurrence of a theoretical break-though. Thebreak-through is referred to as theoretical because it is based upon thecalculated value including the safety factor, so the threshold valueshould be reached before any actual break-through of NO₂ occurs.

Characterization of reactors can be accomplished by testing astatistical sampling of each manufactured batch of reactors to failure,averaging the volume of NO₂ converted to NO before reaching abreak-through limit or consumable reactant exhaustion, and applying asuitable safety factor to adjust for both the statistical dispersionand/or variation of the measurements and variability in component andmanufacturing tolerances, as well as an applicable additional safetymargin to allow for example time to reach a reactor and perform thenecessary replacement before actual break-through would occur.

Principles and embodiments of the present invention also relate to amethod of determining the consumable reactant exhaustion of a conversionreactor comprising measuring an amount of reactant gas that can beconverted into a product gas by a predetermined amount of consumablereactant material, determining the amount of consumable reactantmaterial in a conversion reactor, monitoring the amount of reactant gasflowing into the conversion reactor over time with a flow meter,communicating the amount of gas to a computer configured to record anddisplay the amount of gas that has entered the conversion reactor, andtriggering an alarm when the amount of gas that has entered theconversion reactor equals or exceeds the amount of reactant gas that canbe converted into a product gas by amount of consumable reactantmaterial in a conversion reactor.

Principles and embodiments of the present invention also relate to amethod of halting the flow of toxic gases to a recipient in response tothe presence of toxic gas components by detecting either the presencesof toxic gas entering the delivery conduit or a failure of a conversionreactor to properly function, or both, by one or more sensor(s),communicating a signal from the one or more sensor(s) to a computerindicating reactor failure or toxic gas presence, communicating a signalto a gas regulating device, and halting the flow of toxic gas to thedelivery conduit by communicating a signal to the gas regulating devicethat changes the device from flow configuration to a no-flowconfiguration.

In a non-limiting example illustrated in FIG. 15, a sample probe 730,which may be a cannula, can be positioned in the internal volume 150 atthe outlet end of the reactor 100. The sample probe 740 may be locatedin the exiting gas flow, so that exiting gas components may enter thesample probe and be conveyed to a meter, for example a gaschromatograph, for qualitative and/or quantitative analysis. When NO₂passes through the conversion media unreacted, the NO₂ reaches theoutlet end of the reactor and at least a portion of the exiting gas issampled by the sample probe and measured by the gas chromatographindicating NO₂ is leaving the cartridge. The cannula sensor probe 730can be inserted into the reactor 100 through an opening in the annularwall 110 of the body, and configured to receive at least a portion ofthe gas within the cartridge. The cannula can be connected to an influid communication with a meter (e.g., gas chromatograph) formeasurement of the gas components of interest. The gas transport line740 can receive samples of the gas entering sample probe 730, forexample under pressure, and communicate the gas to a gas chromatograph700 for component detection and concentration measurement, for examplepeak height and retention time, as would be known in the art ofchromatographic analysis. Detection of a characteristic detection peakto indicate the presence of particular gas components (e.g., NO₂) couldbe communicated over a communication path 790 to a computer 800 fordisplay, triggering an alarm, or both. In an embodiment, the sampleprobe 730, gas chromatograph 700, and computer 800 may be configured todetect a concentration of 0.1 ppm NO₂ or greater in the gas streamexiting the conversion reactor, or a concentration of 1.0 ppm NO₂ orgreater in the gas stream.

It is to be understood that the invention is not limited to the detailsof construction or process steps set forth in the above description. Theinvention is capable of other embodiments and of being practiced orbeing carried out in various ways.

Various exemplary embodiments of the invention are described in moredetail with reference to the figures. It should be understood that thesedrawings only illustrate some of the embodiments, and do not representthe full scope of the present invention for which reference should bemade to the accompanying claims.

Various exemplary embodiments of the invention can be used to delivertherapeutic gas to patients suffering from chronic obstructive pulmonarydisease (COPD), idiopathic pulmonary fibrosis (IPF), and pulmonaryhypertension (PH), cystic fibrosis (CF), to name a few. At times, thename of a specific disease may not be provided; however, this is merelyfor ease.

Although the invention herein has been described with reference toparticular embodiments, it is to be understood that these embodimentsare merely illustrative of the principles and applications of thepresent invention. It will be apparent to those skilled in the art thatvarious modifications and variations can be made to the devices,systems, and methods of the present invention without departing from thespirit and scope of the invention. Thus, it is intended that the presentinvention include modifications and variations that are within the scopeof the appended claims and their equivalents.

Reference throughout this specification to “one embodiment,” “certainembodiments,” “one or more embodiments” or “an embodiment” means that aparticular feature, structure, material, or characteristic described inconnection with the embodiment is included in at least one embodiment ofthe invention. Thus, the appearances of the phrases such as “in one ormore embodiments,” “in certain embodiments,” “in one embodiment” or “inan embodiment” in various places throughout this specification are notnecessarily referring to the same embodiment of the invention.Furthermore, the particular features, structures, materials, orcharacteristics may be combined in any suitable manner in one or moreembodiments.

What is claimed is:
 1. A system for safely delivering a supply of nitricoxide (NO) to a recipient, comprising: a gas source that supplies a gas,wherein the gas supplied by the gas source is nitrogen dioxide (NO₂); agas conduit connected to and in fluid communication with the gas source;a NO₂-to-NO reactor cartridge connected to and in fluid communicationwith the gas conduit, so as to allow gas to flow from the gas source toan inlet end of the NO₂-to-NO reactor cartridge, wherein the NO₂-to-NOreactor cartridge comprises a consumable conversion media; one or moresensor probe(s) configured to monitor functioning of the NO₂-to-NOreactor cartridge operatively associated with the NO₂-to-NO reactorcartridge, wherein the one or more sensor probe(s) are embedded into theconsumable conversion media and the one or more sensor probe(s) is amoisture sensor configured to determine an amount of moisture present inthe consumable conversion media; a delivery conduit connected to and influid communication with an outlet end of the NO₂-to-NO reactorcartridge, wherein the delivery conduit is operable to allow NO gas fromthe NO₂-to-NO reactor cartridge to flow to the recipient; a computer inelectronic communication with the one or more sensor probe(s) over acommunication path, wherein the computer is configured to receiveelectronic signals from the one or more sensor probe(s) and calculate aperformance value; and a regulating means in electronic communicationwith the computer over a communication path, wherein the regulatingmeans is controlled based on the performance value.
 2. The system ofclaim 1, further comprises a flow meter for measuring an amount of gasentering the NO₂-to-NO reactor cartridge.
 3. The system of claim 1,further comprises a flow meter for measuring an amount of gas beingdelivered to the recipient.
 4. The system of claim 1, further comprisesan NO₂ sensor operationally associated with the delivery conduitconfigured to a presence of an unacceptable level of NO₂ in the gasbeing directed to the recipient.
 5. The system of claim 1, wherein theperformance value is calculated and utilized for comparison with apredetermined threshold value, the computer is configured to generate anactuating signal when the performance value falls below the thresholdvalue, and the regulating means is configured to receive the actuatingsignal from the computer, wherein the regulating means is configured tohalt the delivery of the gas to a recipient when the actuating signal isreceived from the computer.
 6. The system of claim 5, wherein thethreshold value indicates that a predetermined amount of the consumableconversion media has been reached, and wherein the computer isconfigured to alert a user through a display, an audible alarm, or boththat the NO₂-to-NO reactor cartridge is exhausted or compromised.
 7. Thesystem of claim 1, wherein the one or more sensor probe(s) is configuredto further detect or measure the concentration of ascorbic acid, theconcentration of dehydroascorbic acid, the concentration of water (H₂O),the concentration of NO₂, the concentration of NO, the concentration ofO₂, the concentration of HNO₃, the pH of at least a portion of theNO₂-to-NO reactor cartridge, the redox potentials of chemical species inthe NO₂-to-NO reactor cartridge, the mass flow rate of gases, theconductance at the surface of the silica gel, or combinations thereof.8. A method of monitoring the performance of a nitrogen dioxide(NO₂)-to-nitric oxide (NO) reactor cartridge, the method comprising:incorporating one or more sensor probe(s) into an NO₂-to-NO reactorcartridge comprising a conversion media, wherein the one or more sensorprobe(s) are operatively associated with the NO₂-to-NO reactor cartridgeand the one or more sensor probe(s) is a moisture sensor configured todetermine the amount of moisture present in the conversion media; andoperatively associating at least one meter with the one or more sensorprobe(s) and wherein the one or more sensor probe(s) are embedded intothe conversion media; calculating a performance value based onelectronic signals from the one or more sensor probe(s); and controllinga regulating means based on the performance value.
 9. The method ofclaim 8, which further comprises incorporating the NO₂-to-NO reactorcartridge into an NO delivery system, wherein the NO₂-to-NO reactorcartridge is connected to and in fluid communication with a gas sourceconduit that is configured to contain and direct a gas from a gas sourceto the NO₂-to-NO reactor cartridge.
 10. The method of claim 9, whichfurther comprises detecting physical and/or chemical characteristics ofthe conversion media with the one or more sensor probe(s); measuring thedetected physical and/or chemical characteristics with the operativelyassociated meter; communicating the measured physical and/or chemicalcharacteristics to a computer; and monitoring the communicatedcharacteristics with the computer.
 11. The method of claim 8, whereinthe conversion media comprises a packing material coated with ascorbicacid, alpha tocopherol, or gamma tocopherol, and a color agent.
 12. Asystem for safely delivering a supply of nitric oxide (NO) to arecipient, comprising: a gas source that supplies a gas, wherein the gasis nitrogen dioxide (NO₂) or NO; a gas conduit connected to and in fluidcommunication with the gas source; a NO₂-to-NO reactor cartridgeconnected to and in fluid communication with the gas conduit, so as toallow gas to flow from the gas source to an inlet end of the NO₂-to-NOreactor cartridge, wherein the NO₂-to-NO reactor cartridge comprises aconsumable conversion media; one or more sensor probe(s) configured tomonitor functioning of the NO₂-to-NO reactor cartridge operativelyassociated with the NO₂-to-NO reactor cartridge, wherein the one or moresensor probes are embedded into the consumable conversion media and theone or more sensor probe(s) is a moisture sensor configured to determinean amount of moisture present in the consumable conversion media; adelivery conduit connected to and in fluid communication with an outletend of the NO₂-to-NO reactor cartridge, wherein the delivery conduit isoperable to allow NO gas from the NO₂-to-NO reactor cartridge to flow tothe recipient; a computer in electronic communication with the one ormore sensor probe(s) over a communication path, wherein the computer isconfigured to receive electronic signals from the one or more sensorprobe(s) and calculate a performance value for comparison with apredetermined threshold value, and configured to generate an actuatingsignal when the performance value falls below the threshold value; and aregulating means in electronic communication with the computer over acommunication path, wherein the regulating means is configured toreceive the actuating signal from the computer, and wherein theregulating means halts the delivery of the gas to a recipient.
 13. Thesystem of claim 12, wherein the NO₂-to-NO reactor cartridge comprises anouter reactor shell, an inlet, an outlet, and the consumable conversionmedia including solid packing material coated with consumable reactant.14. The system of claim 12, wherein the gas source is encased within anouter housing.